This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Overview: The promise of improved MRI results at high field strength is compromised by the difficulties encountered at high field, including: i) Non-uniform excitation, due to the non-uniform B1 field inherent at high field. Typically, the non-uniform excitation produces non-uniform tissue contrast, although other deleterious effects can be produced as well. ii) Large susceptibility gradients, which can distort slice positions unless large slice-select gradients are used. However, the limited RF power available on high field systems severely limits the gradient strength that can be used for T2-weighted images. The specific aims propose the further development and refinement of two new RF pulse designs to ameliorate these deleterious effects. In addition, further development of software for simulating MRI experiments is proposed to aid in effective implementation of these new RF pulses into suitably re-designed MRI experiments. Specific aim 1: Pulses with immunity to B1 inhomogeneity. The new B1-insensitive design is based on optimized concatenations of rectangular pulses applied along different axes in the rotating frame, where the optimization is for both uniform tip and immunity to resonance offset. The design focuses on excitation pulses, but includes extension of the method to spin echo and inversion pulses. Specific aim 2: Lowered peak voltage spin echo frequency-selective pulses. The new, lowered peak voltage design method consists of concatenation of conventional, frequency-selective pulses with gradients of alternating sign. The design includes spoiler gradients incorporated into the spin echo pulse to shorten the overall length of the pulse. Operation of these pulses in inhomogeneous B1 fields is also considered. Specific aim 3: Further development of MRI simulation software with inclusion of "inadvertent" magnetization transfer (MT) effects. The further development builds on software already developed for MP RAGE MRI experiments, and will include extended phase graph (EPG) algorithms to cover a wide range of MRI experiments. These simulations will aid in effective implementation of the new RF pulses, and avoid deleterious MT effects. A further use of these simulations is expected to be in the optimization of MRI sequences for 4.0 Tesla. New specific aim 4. The pulses generated from specific aim 1 generate considerably more SAR and MT effects (specific aim 3) than the pulses they replace. In order to not prolong the acquisition time for the MRI experiment, a greater amount of k-space data must be collected following each RF pulse. We propose to make use of spiral gradient readouts to accomplish this. However, spiral gradient waveforms require corrections for gradient infidelity (e.g., eddy currents) and for incorrect gradient timings to avoid image blurring. In addition, corrections for sample resonance offsets are required. Specific aim 4 proposes to develop simulations for spiral gradients, with the ability to add gradient imperfections and resonance offsets, to investigate the degree to which gradient imperfections and resonance offsets need to be corrected to prevent significant image blurring. The initial simulations will be aimed at 3D MPRAGE experiments. New specific aim 5. With the aid of the simulations of specific aim 4, we propose to evaluate and possibly extend recently published methods to ameliorate the effects of gradient imperfections and resonance offsets. This includes methods to measure gradient imperfections and sample resonance offsets. We expect the correction algorithms will eventually have to be migrated to the CIND's multiprocessor computer to enable de-blurred images to be generated in a timely manner.